Evaluation of Nanoparticle Tracking Analysis for the Detection of Rod-Shaped Particles and Protein Aggregates
Evaluation of Nanoparticle Tracking Analysis for the Detection of Rod-Shaped Particles and Protein Aggregates
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DOI：
10.1016/j.xphs.2019.10.006
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发表时间：
2020-01-01
影响因子：
3.8
通讯作者：
Murphy, Regina M.
中科院分区：
文献类型：
--
作者：
Hoover, Brandon M.;Murphy, Regina M.
纳米颗粒跟踪分析（NTA）是测量包括脂质体和病毒在内的球状生物颗粒流体动力学尺寸的重要技术。尽管棒状颗粒的NTA引起了相当大的兴趣，但对它们的关注却很少。例如，淀粉样原纤维和原原纤维是具有棒状形态的蛋白质聚集体，直径为2- 15nm，长度为50 nm至1 μ m，与阿尔茨海默氏症和帕金森病等疾病有关。我们使用NTA测量了金纳米棒（直径10 nm，长度35-250 nm）和肌球蛋白（直径2 nm，长度160 nm）的浓度和水动力学尺寸，作为棒状颗粒的模型。只要控制颗粒浓度和溶液条件，金纳米棒的水动力直径测量值与理论计算值一致。肌球蛋白单体不可见的NTA，但检测到一个小群体的聚集体。我们将NTA结果与其他光散射数据相结合，以深入了解含有单体和聚集体的蛋白质溶液的数量和大小分布。最后，我们通过表征α -突触核蛋白的聚集，证明了NTA的效用及其局限性。值得注意的是，NTA通过分析流体动力尺寸与强度的比率来检测从致密到拉长的形态变化。(C) 2020美国药剂师协会(R)。Elsevier Inc.出版。版权所有。
Nanoparticle tracking analysis (NTA) is an important technique for measuring hydrodynamic size of globular biological particles including liposomes and viruses. Less attention has been paid to NTA of rod-like particles, despite their considerable interest. For example, amyloid fibrils and protofibrils are protein aggregates with rod-like morphology, diameters of 2-15 nm, and lengths from 50 nm to 1 mu m, and linked to diseases including Alzheimer's and Parkinson's. We used NTA to measure the concentration and hydrodynamic size of gold nanorods (10 nm diameter, 35-250 nm length) and myosin (2 nm diameter, 160 nm length), as models of rod-like particles. Measured hydrodynamic diameters of gold nanorods were consistent with theoretical calculations, as long as particle concentration and solution conditions were controlled. Myosin monomers were invisible by NTA, but a small population of aggregates was detected. We combined NTA results with other light scattering data to gain insight into number and size distribution of protein solutions containing both monomer and aggregates. Finally, we demonstrated the utility of NTA and its limitations by characterizing aggregates of alpha-synuclein. Of note is the use of NTA to detect a change in morphology from compact to elongated by analyzing the ratio of hydrodynamic size to intensity. (C) 2020 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.